USPTO Patents Application 09993647

United States Patent and Trademark Office

UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450

Alexandria, Virginia 223 1 3- 1450
www.usplo.gov

APPLICATION NO.

FILING DATE

FIRST NAMED INVENTOR

ATTORNEY DOCKET NO.

CONFIRMATION NO.

09/993,647

11/27/2001

Bemd Riedl

BAYER 18A

1010

23599 7590 06/29/2006

MILLEN, WHITE, ZELANO & BRANIGAN, P.C.
2200 CLARENDON BLVD.
SUITE 1400

ARLINGTON, VA 22201

EXAMINER

RAO, DEEPAK R

ART UNIT

PAPER NUMBER

1624

DATE MAILED: 06/29/2006

Please find below and/or attached an Office communication concerning this application or proceeding.

PTO-90C (Rev. 10/03)

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Application No.

09/993,647

Applicant(s)
RIEDLETAL

Examiner

Deepak Rao

Art Unit

1624

- The MAILING DATE of this communication appears on the cover sheet with the correspondence address -
Period for Reply

A SHORTENED STATUTORY PERIOD FOR REPLY IS SET TO EXPIRE 3 MONTH(S) OR THIRTY (30) DAYS,

WHICHEVER IS LONGER, FROM THE MAILING DATE OF THIS COMMUNICATION.

- Extensions of time may be available under the provisions of 37 CFR 1.136(a). In no event, however, may a reply be timely filed
after SIX (6) MONTHS from the mailing date of this communication.

- If NO period for reply is specified above, the maximum statutory period will apply and will expire SIX (6) MONTHS from the mailing date of this communication.

- Failure to reply within the set or extended period for reply will, by statute, cause the application to become ABANDONED (35 U.S.C. § 133).
Any reply received by the Office later than three months after the mailing date of this communication, even if timely filed, may reduce any
earned patent term adjustment. See 37 CFR 1 .704(b).

Status

1 )S Responsive to communication(s) filed on 13 September 2005 .
2a)D This action is FINAL. 2b)S This action is non-final.

3) D Since this application is in condition for allowance except for formal matters, prosecution as to the merits is

closed in accordance with the practice under Ex parte Quayle, 1935 CD. 1 1, 453 O.G. 213.

Disposition of Claims

4) ^3 Claim(s) 74.81.87.93 and 99-116 %lare pending in the application.

4a) Of the above claim(s) is/are withdrawn from consideration.

5) Q Claim(s) is/are allowed.

6) EI Claim(s) 74.81.87.93 and 99-116 tolare rejected.

7) 0 Claim(s) is/are objected to.

8) D Claim(s) are subject to restriction and/or election requirement.

Application Papers

£))□ The specification is objected to by the Examiner.

10)D The drawing(s) filed on is/are: a)D accepted or b)D objected to by the Examiner.

Applicant may not request that any objection to the drawing(s) be held in abeyance. See 37 CFR 1 .85(a).

Replacement drawing sheet(s) including the correction is required if the drawing(s) is objected to. See 37 CFR 1 .121 (d).
1 1 )□ The oath or declaration is objected to by the Examiner. Note the attached Office Action or form PTO-1 52.

Priority under 35 U.S.C. § 119

12)D Acknowledgment is made of a claim for foreign priority under 35 U.S.C. § 1 19(a)-(d) or (f).
a)D All b)D Some * c)Q None of:

1 .Q Certified copies of the priority documents have been received.

2. Q Certified copies of the priority documents have been received in Application No. .

3. D Copies of the certified copies of the priority documents have been received in this National Stage

application from the International Bureau (PCT Rule 17.2(a)).
* See the attached detailed Office action for a list of the certified copies not received.

Attachment(s)

1 ) ^ Notice of References Cited (PTO-892) 4) □ Interview Summary (PTO-41 3)

2) □ Notice of Draftsperson's Patent Drawing Review (PTO-948) Paper No(s)/lv1ail Date. .

3) 03 Information Disclosure Statement(s) (PTO-1449 or PTO/SB/08) 5 ) D Notice of Informal Patent Application (PTO-152)

Paper No(syMail Date 20040507& 20040512 . 6) □ Other: .

U.S. Patent and Trademark Office
PTOL-326 (Rev. 7-05)

Office Action Summary

Part of Paper No./Mail Date 20060623

Application/Control Number: 09/993,647 Page 2

Art Unit: 1624

DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.1 14 was filed in this application
after appeal to the Board of Patent Appeals and Interferences, but prior to a decision on the
appeal. Since this application is eligible for continued examination under 37 CFR 1.114 and the
fee set forth in 37 CFR 1 .17(e) has been timely paid, the appeal has been withdrawn pursuant to
37 CFR 1.114 and prosecution in this application has been reopened pursuant to 37 CFR 1.114.
Applicant's submission filed on September 13, 2005 has been entered.

Claims 74, 81, 87, 93 and 99-1 16 are pending in this application.

Claim Rejections - 35 USC§112
The following is a quotation of the first paragraph of 35 U.S.C. 112:

The specification shall contain a written description of the invention, and of the manner and process of making
and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it
pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode
_ contemplated by the inventor of carrying out his invention.

Claims 74, 81, 87, 93 and 99-1 16 are rejected under 35 U.S.C. 1 12, first paragraph,
because the specification, while being enabling for the in vitro treatment of the tumor cell lines
HCT1 16 and DLD-1, does not reasonably provide enablement for a method for the treatment of
all types of solid tumors, carcinomas, myeloid disorders or adenomas. The specification does
not enable any person skilled in the art to which it pertains, or with which it is most nearly
connected, to use the invention commensurate in scope with these claims.

In evaluating the enablement question, several factors are to be considered. Note In re
Wands, 8 USPQ2d 1400 and Ex parte Forman, 230 USPQ 546. The factors include: 1) The

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Art Unit: 1624

nature of the invention, 2) the state of the prior art, 3) the predictability or lack thereof in the
art, 4) the amount of direction or guidance present, 5) the presence or absence of working
examples, 6) the breadth of the claims, and 7) the quantity of experimentation needed. The
determination that "undue experimentation" would have been needed to make and use the
claimed invention is not a single, simple factual determination. Rather, it is a conclusion reached
by weighing all the above noted factual considerations.

The instant claims are drawn to 'a method for the treatment of solid tumor' or 'a method
for the treatment of a carcinoma, myeloid disorder or adenoma' and according to the
specification, the compounds are useful in the treatment of solid cancers such as carcinomas,
myeloid disorders or adenomas, see specification page 2, lines 5-17. First, the instant claims
cover 'solid tumors', 'carcinomas', 'myeloid disorders', and 'adenomas' that are known to exist
and those that may be discovered in the future, for which there is no enablement provided.

Note: Solid tumor is a cancer of body of tissues other than blood, bone marrow or the
lymphatic system. Carcinoma is any cancer that arises from epithelial cells. Myeloid leukemia
is a malignancy of immature bone marrow cells. Adenoma is a collection of growths of
glandular origin.

No compound has ever been found to treat solid tumors, carcinomas, myeloid disorders
or adenomas of all types generally. Since this assertion is contrary to what is known in
medicine, proof must be provided that this revolutionary assertion has merits. The existence of
such a "silver bullet" is contrary to our present understanding of oncology. Cecil Textbook of
Medicine states that "each specific type has unique biologic and clinical features that must be
appreciated for proper diagnosis, treatment and study" (see the enclosed article, page 1004).

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Different types of cancers affect different organs and have different methods of growth and harm
to the body. Also see In re Buting, 163 USPQ 689 (CCPA 1969), wherein 'evidence involving a
single compound and two types of cancer, was held insufficient to establish the utility of the
claims directed to disparate types of cancers'. Thus, it is beyond the skill of oncologists today to
get an agent to be effective against solid tumors, carcinomas, myeloid disorders or adenomas in
general.

In evaluating the enablement question, several factors are to be considered. Note In re
Wands, 8 USPQ2d 1400 and Ex parte Forman, 230 USPQ 546. The factors include: 1) The
nature of the invention, 2) the state of the prior art, 3) the predictability or lack thereof in the
art, 4) the amount of direction or guidance present, 5) the presence or absence of working
examples, 6) the breadth of the claims, and 7) the quantity of experimentation needed.

1) The nature of the invention: Therapeutic use of the compounds in treating several types of
solid cancers, carcinomas, myeloid disorders, and adenomas.

2) The state of the prior art: There are no known compounds of similar structure, which have
been demonstrated to treat all types of the cancers recited in the claims. Stein (document
enclosed) provides that "the physician's approach to the treatment of patients with cancer varies
depending on the following features: organ of origin, histology and stage, paraneoplastic
syndromes, age of the patient and presence of other morbid diseases" (see page 707). Further,
the reference provides that "Cancer represents hundreds of diseases with many causes. Although
each disease may share certain general features with others, the approach to therapy for a give
problem will vary" (see page 708).

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3) The predictability or lack thereof in the art: Applicants have not provided any competent
evidence or disclosed tests that are highly predictive for the pharmaceutical use of the instant
compounds. Pharmacological activity in general is a very unpredictable area. Note that in cases
involving physiological activity such as the instant case, "the scope of enablement obviously
varies inversely with the degree of unpredictability of the factors involved". See In re Fisher,
All F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).

4) The amount of direction or guidance present and 5) the presence or absence of working
examples: There are no doses present to direct one to protect a potential host from the disorders
embraced by the instant claims nor there are doses given for the treatment of the disorders
recited. The specification provides assays (see pages 94-96) to test the compounds in vitro and
discloses that the compounds exhibit RAF kinase inhibitory properties. However, there is no
demonstrated correlation that the tests and results apply to all of the disorders embraced by the
instant claims.

6) The breadth of the claims: The instant claims embrace the treatment of all types of solid
tumors, carcinomas, myeloid disorders and adenomas. See In re Vaeck, 947 F.2d 488, 495, 20
USPQ2d 1438, 1444 (Fed. Cir. 1991).

7) The quantity of experimentation needed would be an undue burden to one skilled in the
pharmaceutical arts since there is inadequate guidance given to the skilled artisan, regarding the
pharmaceutical use, for the reasons stated above. The state of the art provides that "Adult acute
myeloid leukemia (AML) and the myelodysplasia syndromes (MDS) remain a formidable
therapeutic challenge" (see Crump, Medline Abstract).

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Thus, factors such as "sufficient working examples", "the level of skill in the art" and
"predictability", etc. have been demonstrated to be sufficiently lacking in the use of the
invention. In view of the breadth of the claim, the chemical nature of the invention, the
unpredictability of ligand-receptor interactions in general, and the lack of working examples
regarding the activity of the claimed compounds, one having ordinary skill in the art would have
to undergo an undue amount of experimentation to use the invention commensurate in scope
with the claims.

Double Patenting

The nonstatutory double patenting rejection is based on a judicially created doctrine
grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or
improper timewise extension of the "right to exclude" granted by a patent and to prevent possible
harassment by multiple assignees. A nonstatutory obviousness-type double patenting rejection
is appropriate where the conflicting claims are not identical, but at least one examined
application claim is not patentably distinct from the reference claim(s) because the examined
application claim is either anticipated by, or would have been obvious over, the reference
claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re
Goodman, 1 1 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225
USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re
Vogel, All F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163
USPQ 644 (CCPA 1969).

A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may
be used to overcome an actual or provisional rejection based on a nonstatutory double patenting
ground provided the conflicting application or patent either is shown to be commonly owned
with this application, or claims an invention made as a result of activities undertaken within the
scope of a joint research agreement.

Effective January 1, 1994, a registered attorney or agent of record may sign a terminal
disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR
3.73(b).

1. Claims 74, 81, 87, 93 and 99-1 16 are provisionally rejected under the judicially created

doctrine of obviousness-type double patenting as being unpatentable over claims 67, 73, 78, and

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83 of copending Application No. 10/042,226. Although the conflicting claims are not identical,
they are not patentably distinct from each other because the instantly claimed methods of use of
the compounds are substantially embraced by the reference claims. The reference claims are
also drawn to a method for the treatment of cancers including carcinomas, myeloid disorders,
adenomas, using phenyl urea compounds, which include the compounds recited in the instant
claims. One of ordinary skill in the art would have been motivated to select the compounds of
the instant claims from the list of compounds recited in reference claims because such
compounds would have been suggested by the reference as a whole because the skilled artisan
would have had reasonable expectation that any of the compounds would have had the same use
taught for the genus as a whole.

This is a provisional obviousness-type double patenting rejection because the conflicting
claims have not in fact been patented.

2. Claims 74, 81, 87, 93 and 99-1 16 are provisionally rejected under the judicially created
doctrine of obviousness-type double patenting as being unpatentable over claim 67 of copending
Application No. 09/948,915. Although the conflicting claims are not identical, they are not
patentably distinct from each other because the instantly claimed methods of use of the
compounds are substantially embraced by the reference claims. The reference claim is also
drawn to a method for the treatment of cancerous cell growth using phenyl urea compounds,
which according to the reference disclosure includes treatment of solid tumors, carcinomas,
myeloid disorders, adenomas. The reference claimed method recites a list of compounds that are
used in the method, which includes the use of compounds recited in the instant claims. One of

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ordinary skill in the art would have been motivated to select the compounds of the instant claims
from the list of compounds recited in reference claims because such compounds would have
been suggested by the reference as a whole because the skilled artisan would have had
reasonable expectation that any of the compounds would have had the same use taught for the
genus as a whole.

This is a provisional obviousness- type double patenting rejection because the conflicting
claims have not in fact been patented.

3. Claims 74, 81, 87, 93 and 99-1 16 are provisionally rejected under the judicially created
doctrine of obviousness-type double patenting as being unpatentable over claims 1, 36 and 40 of
copending Application No. 10/361,850. Although the conflicting claims are not identical, they
are not patentably distinct from each other because the instantly claimed methods of use of the
compounds are substantially embraced by the reference claims. The reference claims are also
drawn to a method for the treatment of raf-mediated disorders, which include tumor growth, etc.
using a generic group phenyl urea compounds. The reference genus includes the compounds
recited in the instant claims. One of ordinary skill in the art would have been motivated to select
the compounds of the instant claims from generic group of compounds recited in reference
claims because such compounds would have been suggested by the reference as a whole because
the skilled artisan would have had reasonable expectation that any of the compounds would have
had the same use taught for the genus as a whole.

This is a provisional obviousness-type double patenting rejection because the conflicting
claims have not in fact been patented.

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Information Disclosure Statement
Receipt is acknowledged of the Information Disclosure Statement filed on May 7, 2004
and May 12, 2004 and copies are enclosed herewith. Applicant's attention is directed to the IDS
filed on May 7, 2004 wherein each of the sheets were identified as "Sheet 1 or 18"; "Sheet 5 of
18"; "Sheet 9 of 18"; "Sheet 17 of 18"; and "Sheet 18 of 18", however, there were only five (5)
PTO-1449 sheets found, which are renumbered as sheets 1 through 5 of 5.

Conclusion

Any inquiry concerning this communication or earlier communications from the
examiner should be directed to Deepak Rao whose telephone number is (571) 272-0672. The
examiner can normally be reached on Tuesday-Friday from 6:30am to 5:00pm.

If attempts to reach the examiner by telephone are unsuccessful, the examiner's
supervisor, James O. Wilson, can be reached at (571) 272-0661 . The fax phone number for the
organization where this application or proceeding is assigned is (571) 273-8300.

Any inquiry of a general nature or relating to the status of this application or proceeding
should be directed to the receptionist whose telephone number is (571) 272-1600.

Information regarding the status of an application may be obtained from the Patent
Application Information Retrieval (PAIR) system. Status information for published applications
may be obtained from either Private PAIR or Public PAIR. Status information for unpublished
applications is available through Private PAIR only. For more information about the PAIR

Application/Control Number: 09/993,647
Art Unit: 1624

Page 10

system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR
system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).

Deepak Rao
Primary Examiner
Art Unit 1624

June 23, 2006